Multi-scale approaches to Food Sciences: computational QM and MM explorations at the microscopic level

L'obiettivo principale della politica di sicurezza alimentare è quello di garantire la salute dei consumatori attraverso regole e protocolli di sicurezza specifici. Al fine di rispondere ai requisiti di sicurezza alimentare e standardizzazione della qualità, nel 2002 il Parlamento Europeo e il Consiglio dell'UE (Regolamento (CE) 178/2002 (CE, 2002)), hanno cercato di uniformare concetti, principi e procedure in modo da fornire una base comune in materia di disciplina degli alimenti e mangimi provenienti da Stati membri a livello comunitario. La formalizzazione di regole e protocolli di standardizzazione dovrebbe però passare attraverso una più dettagliata e accurata comprensione ed armonizzazione delle proprietà globali (macroscopiche), pseudo-locali (mesoscopiche), ed eventualmente, locali (microscopiche) dei prodotti alimentari. L'obiettivo principale di questa tesi di dottorato è di illustrare come le tecniche computazionali possano rappresentare un valido supporto per l'analisi e ciò tramite (i) l’applicazione di protocolli e (ii) miglioramento delle tecniche ampiamente applicate. Una dimostrazione diretta delle potenzialità già offerte dagli approcci computazionali viene offerta nel primo lavoro in cui un virtual screening basato su docking è stato applicato al fine di valutare la preliminare xeno-androgenicità di alcuni contaminanti alimentari. Il secondo e terzo lavoro riguardano lo sviluppo e la convalida di nuovi descrittori chimico-fisici in un contesto 3D-QSAR. Denominata HyPhar (Hydrophobic Pharmacophore), la nuova metodologia così messa a punto è stata usata per esplorare il tema della selettività tra bersagli molecolari strutturalmente correlati e ha così dimostrato di possedere i necessari requisiti di applicabilità e adattabilità in un contesto alimentare. Nel complesso, i risultati ci permettono di essere fiduciosi nel potenziale impatto che le tecniche in silico potranno avere nella identificazione e chiarificazione di eventi molecolari implicati negli aspetti tossicologici e nutrizionali degli alimenti.

UMA ALIANÇA ABOMINÁVEL E PER/VERTIDA? ANOTAÇÕES SUBALTERNAS SOBRE O ARQUIVO DEUTERONÔMICO

O objetivo central desta pesquisa é avaliar os valores e possibilidades da aliança pregada no Deuteronômio. Para tanto, procuro captar a necessária tensão de qualquer tipo de aliança. Faço esse exercício, primeiramente, no próprio campo da hermenêutica. Sugiro uma leitura subalterna que agregue diferentes lutas no interior das interpretações libertárias (feminista, queer e pós-colonial). Nesse ínterim, forjo o trabalho do exegeta orgânico , a saber, aquele intérprete que articula vozes dissidentes para fazer frente às estruturas sistêmicas de subordinação. Após essa proposição teórica, avalio o Deuteronômio enquanto discursos concatenados em forma de arquivo. A principal sugestão é de que os textos deuteronômicos foram coletados ou produzidos em prol de um ideal de berit aliança . Esse ideal origina-se do material agora disposto em 4,44-26+28: um contrato comunitário atávico com Yhvh. Esse resultado é possibilitado pela crítica retórica ao texto e seus interesses propagandísticos desde o nascedouro arquivístico. Após uma comparação honesta com os tratados do Antigo Oriente Próximo, não se pode mais negar a pedagogia da obediência intrínseca ao contrato. A isso chamo, muitas vezes, de colusão do povo santo . A crítica retórica, entretanto, não encaminha apenas uma reificação desse ideal de berit, ao apontar, antes, para o debate interno da comunidade. Um contrato retórico, afinal, guarda em si, memórias silenciadas para que a propaganda se efetive. Nesse momento é que busco colisões de memórias, em especial, dentro das perícopes proibitivas do contrato. Todo o lixo deuteronômico, por assim dizer, está assinalado por duas fórmulas básicas: ki to abat yhvh eis uma abominação para Yhvh e ubi arta ha-ra mi-qirbeka exterminarás o per/vertido do teu meio . Dedico-me aos textos marcados por essas fórmulas, ao fomentar uma episódica unificação de abomináveis e per/vertidos . Avalio a luta particular de cada um/a, para então, propor uma agenda subalterna que promova a justiça social por reconhecimento e redistribuição. A aliança abominável e per/vertida intra-Deuteronômio apresenta uma proposta radicalmente democrática (i) em favor de uma cultura aberta ao Outro e (ii) contra estruturas autoritárias piramidais. Assinalo, portanto, que com essa dupla tática, os valores imperiais de hierarquização e subtração da irmandade deuteronômica são retoricamente postos em debate na comunidade.

In search of a sustainable success strategy in the Chinese chemical industry

The Chinese chemical industry is facing fierce competition and changing market dynamics due to the change in the country's economic policy. Its government has applied administr.ttive actions rather than simply relying on the market to address the changing dynamics. It has attempted to privatise government-owned enterprises by corporatisation coupled with industrial restructuring. This paper uses a case study of Peony Printing Ink Co Ltd, a state-owned chemical enterprise, to illustrate the effectiveness of developing internal competences to improve long-term operational performance rather than the adoption of a privatisation approach.

Chemical and physical methods of enhancing the percutaneous absorption of antimicrobial agents

Contrary to previously held beliefs, it is now known that bacteria exist not only on the surface of the skin but they are also distributed at varying depths beneath the skin surface. Hence, in order to sterilise the skin, antimicrobial agents are required to penetrate across the skin and eliminate the bacteria residing at all depths. Chlorhexidine is an antimicrobial agent with the widest use for skin sterilisation. However, due to its poor permeation rate across the skin, sterilisation of the skin cannot be achieved and, therefore, the remaining bacteria can act as a source of infection during an operation or insertion of catheters. The underlying theme of this study is to enhance the permeation of this antimicrobial agent in the skin by employing chemical (enhancers and supersaturated systems) or physical (iontophoresis) techniques. The hydrochloride salt of chlorhexidine (CHX), a poorly soluble salt, was used throughout this study. The effect of ionisation on in vitro permeation rate across the excised human epidennis was investigated using Franz-type diffusion cells. Saturated solutions of CHX were used as donor and the variable studied was vehicle pH. Permeation rate was increased with increasing vehicle pH. The pH effect was not related to the level of ionisation of the drug. The effect of donor vehicle was also studied using saturated solutions of CHX in 10% and 20% ethanol as the donor solutions. Permeation of CHX was enhanced by increasing the concentration of ethanol which could be due to the higher concentration of CHX in the donor phase and the effect of ethanol itself on the membrane. The interplay between drug diffusion and enhancer pretreatment of the epidennis was studied. Pretreatment of the membrane with 10% Azone/PG demonstrated the highest diffusion rate followed by 10% olcic acid/PG pretreatment compared to other pretreatment regimens (ethanol, dimethyl sulfoxide (DMSO), propylene glycol (PG), sodium dodecyl sulphate (SDS) and dodecyl trimethyl ammonium bromide (DT AB). Differential Scanning Calorimetry (DSC) was also employed to study the mode of action of these enhancers. The potential of supersaturated solutions in enhancing percutaneous absorption of CHX was investigated. Various anti-nucleating polymers were screened in order to establish the most effective agent. Polyvinylpyrrolidone (PVP, K30) was found to be a better candidate than its lower molecular weight counterpart (K25) and hydroxypropyl methyleellulose (HPMC). The permeation studies showed an increase in diffusion rate by increasing the degree of saturation. Iontophoresis is a physical means of transdemal drug delivery enhancement that causes an increased penetration of molecules into or through the skin by the application of an electric field. This technique was employed in conjunction with chemical enhancers to assess the effect on CHX permeation across the human epidermis. An improved transport of CHX, which was pH dependant was observed upon application of the current. Combined use of iontophoresis and chemical enhancers further increased the CHX transport indicating a synergistic effect. Pretreatment of the membrane with 10% Azone/PG demonstrated the greatest effect.

A technique to randomise consecutive codons in a sequence of DNA using MAX oligonucleotides

Randomisation of DNA using conventional methodology requires an excess of genes to be cloned, since with randomised codons NNN or NNG/T 64 genes or 32 genes must be cloned to encode 20 amino acids respectively. Thus, as the number of randomised codons increases, the number of genes required to encode a full set of proteins increases exponentially. Various methods have been developed that address the problems associated with excess of genes that occurs due to the degeneracy of the genetic code. These range from chemical methodologies to biological methods. These all involve the replacement, insertion or deletion of codon(s) rather than individual nucleotides. The biological methods are however limited to random insertion/deletion or replacement. Recent work by Hughes et al., (2003) has randomised three binding residues of a zinc finger gene. The drawback with this is the fact that consecutive codons cannot undergo saturation mutagenesis. This thesis describes the development of a method of saturation mutagenesis that can be used to randomise any number of consecutive codons in a DNA strand. The method makes use of “MAX” oligonucleotides coding for each of the 20 amino acids that are ligated to a conserved sequence of DNA using T4 DNA ligase. The “MAX” oligonucleotides were synthesised in such a way, with an MlyI restriction site, that restriction of the oligonucleotides occurred after the three nucleotides coding for the amino acids. This use of the MlyI site and the restrict, purify, ligate and amplify method allows the insertion of “MAX” codons at any position in the DNA. This methodology reduces the number of clones that are required to produce a representative library and has been demonstrated to be effective to 7 amino acid positions.

Volcanogenic mineralisation in the limestone lake area, Saskatchewan, Canada

This thesis describes the geology, geochemistry and mineralogy of a Lower Proterozoic, metamorphosed volcanogenic Cu-Zn deposit, situated at the western end of the Flin Flon greenstone belt. Stratabound copper mineralisation occurs in silicified and chloritoid-bearing alteration assemblages within felsic tuffs and is mantled by thin (< 3m) high-grade sphalerite layers. Mineralisation is underlain by garnet-hornblende bearing Lower Iron Formation (LIF), and overlain by garnet-grunerite bearing Upper Iron Formation (UIF). Distinctive trace element trends, involving Ti and Zr, in mineralised and footwall felsic tuffs are interpreted to have formed by fractionation associated with a high-level magma chamber in a caldera-type environment. Discrimination diagrams for basaltic rocks are interpreted to indicate their formation in an environment similar to that of recent, primitive, tholeiitic island arcs. Microprobe studies of key mineral phases demonstrate large and small scale chemical variations in silicate phases related to primary lithological, rather than metamorphic, controls. LIF is characterised by alumino-ferro-tschermakite and relatively Mn-poor, Ca-rich garnets, whereas UIF contains manganoan grunerite and Mn-rich garnets. Metamorphic mineral reactions are considered and possible precursor assemblages identified for garnet-, and chloritoid-bearing rocks. Chloritoid-bearing rocks are interpreted as the metamorphosed equivalents of iron-rich feeder zones formed near the surface. The iron-formations are thought to represent iron-rich sediments formed on the sea floor formed from the venting of the ore fluids. Consideration of various mineral assemblages leads to an estimate for peak metamorphic conditions of 450-500oC and > 4Kb total pressure. Comparisons with other volcanogenic deposits indicate affinities with deposits of `Mattabi-type' from the Archean of Ontario. An extrapolation of the main conclusions of the thesis to adjacent areas points to the presence of a number of geologically similar localities with potential for mineralisation.

Statnote 32 : the partial correlation coefficient

In previous statnotes, the application of correlation and regression methods to the analysis of two variables (X,Y) was described. The most important statistic used to measure the degree of correlation between two variables is Pearson’s ‘product moment correlation coefficient’ (‘r’). The correlation between two variables may be due to their common relation to other variables. Hence, investigators using correlation studies need to be alert to the possibilities of spurious correlation and the methods of ‘partial correlation’ are one method of taking this into account. This statnote applies the methods of partial correlation to three scenarios. First, to a fairly obvious example of a spurious correlation resulting from the ‘size effect’ involving the relationship between the number of general practitioners (GP) and the number of deaths of patients in a town. Second, to the relationship between the abundance of the nitrogen-fixing bacterium Azotobacter in soil and three soil variables, and finally, to a more complex scenario, first introduced in Statnote 24involving the relationship between the growth of lichens in the field and climate.

An enhanced functional ability questionnaire (faVIQ) to measure the impact of rehabilitation services on the visually impaired

AIM To develop a short, enhanced functional ability Quality of Vision (faVIQ) instrument based on previous questionnaires employing comprehensive modern statistical techniques to ensure the use of an appropriate response scale, items and scoring of the visual related difficulties experienced by patients with visual impairment. METHODS Items in current quality-of-life questionnaires for the visually impaired were refined by a multi-professional group and visually impaired focus groups. The resulting 76 items were completed by 293 visually impaired patients with stable vision on two occasions separated by a month. The faVIQ scores of 75 patients with no ocular pathology were compared to 75 age and gender matched patients with visual im pairm ent. RESULTS Rasch analysis reduced the faVIQ items to 27. Correlation to standard visual metrics was moderate (r=0.32-0.46) and to the NEI-VFQ was 0.48. The faVIQ was able to clearly discriminate between age and gender matched populations with no ocular pathology and visual impairment with an index of 0.983 and 95% sensitivity and 95% specificity using a cut off of 29. CONCLUSION The faVIQ allows sensitive assessm ent of quality-of-life in the visually im paired and should support studies which evaluate the effectiveness of low vision rehabilitation services. © Copyright International Journal of Ophthalmology Press.

The Latest Prague Contributions to Written Cultural Heritage Processing

* The following text has been originally published in the Proceedings of the Language Recourses and Evaluation Conference held in Lisbon, Portugal, 2004, under the title of "Towards Intelligent Written Cultural Heritage Processing - Lexical processing". I present here a revised contribution of the aforementioned paper and I add here the latest efforts done in the Center for Computational Linguistic in Prague in the field under discussion.

An investigation into the comparable effectiveness of two tests of writing administered to college-level English as a Second Language students: The Computerized Placement Test and holistically scored essay exams

This dissertation describes the findings and implications of a correlational analysis. Scores earned on the Computerized Placement Test (CPT), sentence skills, were compared to essay scores of advanced English as a Second Language (ESL) students. As the CPT is designed for native speakers of English, it was hypothesized that it could be an invalid or unreliable instrument for non-native speakers. Florida community college students are mandated to take the CPT to determine preparedness, as are students at many other U.S. and Canadian colleges. If incoming students score low on the CPT, they may be required to take up to three semesters of remedial coursework. It is essential that scores earned by non-native speakers of English accurately reflect their ability level. They constitute a large and growing body of non-traditional students enrolled at community colleges.^ The study was conducted at Miami-Dade Community College, Wolfson Campus, fall 1997. Participants included 106 advanced ESL students who took both the CPT sentence skills test and wrote final essay exams. The essay exams were holistically scored by trained readers. Also, the participants took the Placement Articulation Software Service (PASS) exam, an alternative form of the CPT. Scores on the CPT and essays were compared by means of a Pearson product-moment correlation to validate the CPT. Scores on the CPT and the PASS exam were compared in the same manner to verify reliability. A percentage of appropriate placements was determined by comparing essay scores to CPT cutoff score ranges. Finally, the instruments were evaluated by means of independent-samples t-tests for performance differences between gender, age, and first language groups.^ The results indicate that the CPT sentence skills test is a valid and reliable placement instrument for advanced- level ESL students who intend to pursue community college degrees. The correlations demonstrated a substantial relationship between CPT and essay scores and a marked relationship between CPT and PASS scores. Appropriate placements were made in 86% of the cases. Furthermore, the CPT was found to discriminate equally among the gender, age, and first language groups included in this study. ^

A Look Back To Look Forward: New Patterns In The Supply/Demand Equation In The Lodging Industry

In his dialogue entitled - A Look Back to Look Forward: New Patterns In The Supply/Demand Equation In The Lodging Industry - by Albert J. Gomes, Senior Principal, Pannell Kerr Forster, Washington, D.C. What the author intends for you to know is the following: “Factors which influence the lodging industry in the United States are changing that industry as far as where hotels are being located, what clientele is being served, and what services are being provided at different facilities. The author charts these changes and makes predictions for the future.” Gomes initially alludes to the evolution of transportation – the human, animal, mechanical progression - and how those changes, in the last 100 years or so, have had a significant impact on the hotel industry. “A look back to look forward treats the past as prologue. American hoteliers are in for some startling changes in their business,” Gomes says. “The man who said that the three most important determinants for the success of a hotel were “location, location, location” did a lot of good only in the short run.” Gomes wants to make you aware of the existence of what he calls, “locational obsolescence.” “Locational obsolescence is a fact of life, and at least in the United States bears a direct correlation to evolutionary changes in transportation technology,” he says. “…the primary business of the hospitality industry is to serve travelers or people who are being transported,” Gomes expands the point. Tied to the transportation element, the author also points out an interesting distinction between hotels and motels. In addressing, “…what clientele is being served, and what services are being provided at different facilities,” Gomes suggests that the transportation factor influences these constituents as well. Also coupled with this discussion are oil prices and shifts in transportation habits, with reference to airline travel being an ever increasing method of travel; capturing much of the inter-city travel market. Gomes refers to airline deregulation as an impetus. The point being, it’s a fluid market rather than a static one, and [successful] hospitality properties need to be cognizant of market dynamics and be able to adjust to the variables in their marketplace. Gomes provides many facts and figures to bolster his assertions. Interestingly and perceptively, at the time of this writing, Gomes alludes to America’s deteriorating road and bridge network. As of right now, in 2009, this is a major issue. Gomes rounds out this study by comparing European hospitality trends to those in the U.S.

Application and evaluation of an Institute of Medicine approach to dietary assessment and planning in long -term care

The primary purpose of these studies was to determine the effect of planning menus using the Institute of Medicine's (IOMs) Simple Nutrient Density Approach on nutrient intakes of long-term care (LTC) residents. In the first study, nutrient intakes of 72 subjects were assessed using Dietary Reference Intakes (DRIs) and IOM methodology. The intake distributions were used to set intake and menu planning goals. In the second study, the facility's regular menus were modified to meet the intake goals for vitamin E, magnesium, zinc, vitamin D and calcium. An experiment was used to test whether the modified menu resulted in intakes of micronutrients sufficient to achieve a low prevalence (<3%) of nutrient inadequacies. Three-day weighed food intakes for 35 females were adjusted for day-to-day variations in order to obtain an estimate of long-term average intake and to estimate the proportion of residents with inadequate nutrient intakes. ^ In the first study, the prevalence of inadequate intakes was determined to be between 65-99% for magnesium, vitamin E, and zinc. Mean usual intakes of Vitamin D and calcium were far below the Adequate Intakes (AIs). In the experimental study, the prevalence of inadequacies was reduced to <3% for zinc and vitamin E but not magnesium. The groups' mean usual intake from the modified menu met or exceeded the AI for calcium but fell short for vitamin D. Alternatively, it was determined that addition of a multivitamin and mineral (MVM) supplement to intakes of the regular menu could be used to achieve goals for vitamin E, zinc and vitamin D but not calcium and magnesium. ^ A combination of menu modification and MVM supplementation may be necessary to achieve a low prevalence of micronutrient inadequacies among LTC residents. Menus should be planned to optimize intakes of those nutrients that are low in an MVM, such as calcium, magnesium, and potassium. A MVM supplement should be provided to fill the gap for nutrients not provided in sufficient amounts by the diet, such as vitamin E and vitamin D. ^

The Effect of Sample and Sample Matrix on DNA Processing: Mechanisms for the Detection and Management of Inhibition in Forensic Samples

The presence of inhibitory substances in biological forensic samples has, and continues to affect the quality of the data generated following DNA typing processes. Although the chemistries used during the procedures have been enhanced to mitigate the effects of these deleterious compounds, some challenges remain. Inhibitors can be components of the samples, the substrate where samples were deposited or chemical(s) associated to the DNA purification step. Therefore, a thorough understanding of the extraction processes and their ability to handle the various types of inhibitory substances can help define the best analytical processing for any given sample. A series of experiments were conducted to establish the inhibition tolerance of quantification and amplification kits using common inhibitory substances in order to determine if current laboratory practices are optimal for identifying potential problems associated with inhibition. DART mass spectrometry was used to determine the amount of inhibitor carryover after sample purification, its correlation to the initial inhibitor input in the sample and the overall effect in the results. Finally, a novel alternative at gathering investigative leads from samples that would otherwise be ineffective for DNA typing due to the large amounts of inhibitory substances and/or environmental degradation was tested. This included generating data associated with microbial peak signatures to identify locations of clandestine human graves. Results demonstrate that the current methods for assessing inhibition are not necessarily accurate, as samples that appear inhibited in the quantification process can yield full DNA profiles, while those that do not indicate inhibition may suffer from lowered amplification efficiency or PCR artifacts. The extraction methods tested were able to remove >90% of the inhibitors from all samples with the exception of phenol, which was present in variable amounts whenever the organic extraction approach was utilized. Although the results attained suggested that most inhibitors produce minimal effect on downstream applications, analysts should practice caution when selecting the best extraction method for particular samples, as casework DNA samples are often present in small quantities and can contain an overwhelming amount of inhibitory substances.

Sonho e cura: o culto de Asclépio em Epidauro entre os séculos IV e II a. C.

Profound changes have marked Greek society from the fourth century B.C.. Conquests, wars and epidemics altered drastically the Greek’s posture regarding his public life, his conception of gods and hence the construction of their spaces, whether sacred or profane. Through the fonts, we perceived that the cult of god Asklepeios turned very popular, in this context, for the peculiar way that the god relates to his devotees, through the dreams. We know that the dream was held, for the Greeks, as a space of real existence, it was sacred, and could be accessed in the healing rituals of Asklepios. Our work intends, thereby, to understand the curious and peculiar oniric space, mainly through the inscriptions, architectural structures of the sanctuary and the ancient texts that refer to the context of the period, because we understand that this space was the essential condition for the popularization of the cult, it placed the individual in direct contact with the divinity, a rare closeness between men and gods accepted by the greek imagery until then.

Representative analyses of garnet, plagioclase, orthopyroxene, ilmenite, hornblende and biotite for pre-tectonic mafic and metapelitic rocks in Gjelsvikfjella

A metamorphic petrological study, in conjunction with recent precise geochronometric data, revealed a complex P-T-t path for high-grade gneisses in a hitherto poorly understood sector of the Mesoproterozoic Maud Belt in East Antarctica. The Maud Belt is an extensive high-grade, polydeformed, metamorphic belt, which records two significant tectono-thermal episodes, once towards the end of the Mesoproterozoic and again towards the late Neoproterozoic/Cambrian. In contrast to previous models, most of the metamorphic mineral assemblages are related to a Pan-African tectono-thermal overprint, with only very few relics of late Mesoproterozoic granulite-facies mineral assemblages (M1) left in strain-protected domains. Petrological and mineral chemical evidence indicates a clockwise P-T-t path for the Pan-African orogeny. Peak metamorphic (M2b) conditions recorded by most rocks in the area (T = 709-785 °C and P = 7.0-9.5 kbar) during the Pan-African orogeny were attained subsequent to decompression from probably eclogite-facies metamorphic conditions (M2a). The new data acquired in this study, together with recent geochronological and geochemical data, permit the development of a geodynamic model for the Maud Belt that involves volcanic arc formation during the late Mesoproterozoic followed by extension at 1100 Ma and subsequent high-grade tectono-thermal reworking once during continent-continent collision at the end of the Mesoproterozoic (M1; 1090-1030 Ma) and again during the Pan-African orogeny (M2a, M2b) between 565 and 530 Ma. Post-peak metamorphic K-metasomatism under amphibolite-facies conditions (M2c) followed and is ascribed to post-orogenic bimodal magmatism between 500 and 480 Ma.